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N-methyl-D-aspartate-induced neurotoxicity in the adult rat retina

Published online by Cambridge University Press:  02 June 2009

Renata Siliprandi ,
Roberto Canella ,
Giorgio Carmignoto ,
Nicola Schiavo ,
Anna Zanellato ,
Renzo Zanoni  and
Guido Vantini
Renata Siliprandi
Affiliation:
Fidia Research Laboratories, Abano Terme, Italy
Roberto Canella
Affiliation:
Fidia Research Laboratories, Abano Terme, Italy
Giorgio Carmignoto
Affiliation:
Fidia Research Laboratories, Abano Terme, Italy
Nicola Schiavo
Affiliation:
Fidia Research Laboratories, Abano Terme, Italy
Anna Zanellato
Affiliation:
Fidia Research Laboratories, Abano Terme, Italy
Renzo Zanoni
Affiliation:
Fidia Research Laboratories, Abano Terme, Italy
Guido Vantini
Affiliation:
Fidia Research Laboratories, Abano Terme, Italy
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Abstract

The present study provides evidence that the adult mammalian retina is highly sensitive to the excitotoxic action of NMDA. In particular, we have investigated the effects of a single intravitreal injection of different doses of N-methyl-D-aspartate (NMDA) (2–200 nmoles) on the adult rat retina. Morphological evaluation of transverse sections of retinae demonstrated a dose-dependent loss of cells in the ganglion cell layer (GCL) and a reduction in the thickness of the inner plexiform layer. No obvious alterations were noted in the more distal retinal layers. Quantitative analyses of Nissl-stained whole-mounted retinae revealed that administration of 20 nmoles of NMDA resulted in a 70% loss of cells with a soma diameter greater than 8 μm (presumed retinal ganglion cells); a 20% loss of cells with a soma diameter smaller than 8 μm (presumed displaced amacrine cells) was also observed. In addition, NMDA produced a dose-dependent decrease of retinal choline acetyltransferase (ChAT) activity, suggesting that NMDA affects cholinergic amacrine cells as well. MK-801, a non-competitive NMDA antagonist, completely prevented the NMDA-induced loss of cells in the GCL and blocked, in a dose-dependent manner, the NMDA-induced decrease of ChAT activity. The excitotoxic action of NMDA observed in these experiments is thus likely mediated through the NMDA receptor subtype. This ”in vivo” model may be utilized to identify potential drugs that antagonize or limit the deleterious effects consequent to NMDA receptor overstimulation in the central nervous system.

Keywords

Cholinergic amacrine cellsCholine acetyltransferaseRetinal ganglion cellsN-methyl-D-aspartateMK-801
Type
Research Articles
Information
Visual Neuroscience , Volume 8 , Issue 6 , June 1992 , pp. 567 - 573
Copyright
Copyright © Cambridge University Press 1992

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